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Article ; Online: Rhinorrhea and increased chloride secretion through the CFTR chloride channel-a systematic review.

Eisenhut, Michael

European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery

2023 Volume 280, Issue 10, Page(s) 4309–4318

Abstract: Purpose: Allergic and non-allergic rhinorrhea in the forms of acute or chronic rhinosinusitis can mean a watery nasal discharge that is disabling. Primary objective was to review the evidence supporting the hypothesis that rhinorrhea is due to increased ...

Abstract	Purpose: Allergic and non-allergic rhinorrhea in the forms of acute or chronic rhinosinusitis can mean a watery nasal discharge that is disabling. Primary objective was to review the evidence supporting the hypothesis that rhinorrhea is due to increased chloride secretion through the CFTR chloride channel. Methods: The structure of the evidence review followed the EQUATOR Reporting Guidelines. Databases searched from inception to February 2022 included Pubmed, EMBASE and the Cochrane library using keywords "Rhinorrhea", "chloride", "chloride channel", "CFTR" and "randomized controlled trial". Quality assessment was according to the Oxford Centre for Evidence-based Medicine. Results: 49 articles were included. They included randomized controlled trials out of which subsets of data with the outcome of rhinorrhea on 6038 participants were analysed and in vitro and animal studies. The review revealed that drugs, which activate CFTR are associated with rhinorrhea. Viruses, which cause rhinorrhea like rhinovirus were found to activate CFTR. The chloride concentration in nasal fluid showed an increase in patients with viral upper respiratory tract infection. Increased hydrostatic tissue pressure, which is an activator of CFTR was observed in allergic upper airway inflammation. In this condition exhaled breath condensate chlorine concentration was found to be significantly increased. Drugs, which can reduce CFTR function including steroids, anti-histamines, sympathomimetic and anticholinergic drugs reduced rhinorrhea in randomized controlled trials. Conclusions: A model of CFTR activation-mediated rhinorrhea explains the effectiveness of anticholinergic, sympathomimetic, anti-histamine and steroid drugs in reducing rhinorrhea and opens up avenues for further improvement of treatment by already known specific CFTR inhibitors.
MeSH term(s)	Animals ; Chloride Channels ; Cystic Fibrosis Transmembrane Conductance Regulator ; Chlorides ; Sympathomimetics ; Nasal Mucosa/metabolism ; Randomized Controlled Trials as Topic
Chemical Substances	Chloride Channels ; Cystic Fibrosis Transmembrane Conductance Regulator (126880-72-6) ; Chlorides ; Sympathomimetics
Language	English
Publishing date	2023-06-20
Publishing country	Germany
Document type	Systematic Review ; Journal Article ; Review
ZDB-ID	1017359-6
ISSN	1434-4726 ; 0937-4477
ISSN (online)	1434-4726
ISSN	0937-4477
DOI	10.1007/s00405-023-08067-w
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Article ; Online: The significance of a lack of rhinorrhea in severe coronavirus 19 lung disease.

Eisenhut, Michael

American journal of physiology. Lung cellular and molecular physiology

2021 Volume 320, Issue 6, Page(s) L1194–L1195

MeSH term(s)	Coronavirus ; Coronavirus Infections ; Humans ; Lung ; Pulmonary Edema ; Rhinorrhea
Language	English
Publishing date	2021-06-22
Publishing country	United States
Document type	Letter ; Comment
ZDB-ID	1013184-x
ISSN	1522-1504 ; 1040-0605
ISSN (online)	1522-1504
ISSN	1040-0605
DOI	10.1152/ajplung.00066.2021
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Zs.A 2749: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)

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Article ; Online: Influence of Cigarette Smoke on Results of Hematological and Immunological Investigations in Patients Exposed to Mycobacterium tuberculosis.

Eisenhut, Michael

The Journal of infectious diseases

2020 Volume 223, Issue 5, Page(s) 924

MeSH term(s)	Cigarette Smoking ; Humans ; Mycobacterium tuberculosis ; Smoke/adverse effects ; Tuberculosis, Pulmonary/immunology
Chemical Substances	Smoke
Language	English
Publishing date	2020-07-29
Publishing country	United States
Document type	Letter
ZDB-ID	3019-3
ISSN	1537-6613 ; 0022-1899
ISSN (online)	1537-6613
ISSN	0022-1899
DOI	10.1093/infdis/jiaa452
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Article: The Identification of Native Epitopes Eliciting a Protective High-Affinity Immunoglobulin Subclass Response to Blood Stages of Plasmodium falciparum: Protocol for Observational Studies.

Eisenhut, Michael

JMIR research protocols

2020 Volume 9, Issue 7, Page(s) e15690

Abstract: Background: Antibodies to blood stages protective against complications of Plasmodium falciparum infection were found to be of immunoglobulin G 1 (IgG1) and IgG3 subclasses and of high affinity to the target epitopes. These target epitopes cannot be ... ...

Abstract	Background: Antibodies to blood stages protective against complications of Plasmodium falciparum infection were found to be of immunoglobulin G 1 (IgG1) and IgG3 subclasses and of high affinity to the target epitopes. These target epitopes cannot be characterized using recombinant antigens because of a lack of appropriate glycosylation, phosphorylation, methylation, and bisulfide bond formation, which determine the structure of conformational and nonlinear epitopes within the tertiary and quaternary structures of native P. falciparum antigens. Objective: This study aims to develop a method for the comprehensive detection of all P. falciparum schizont antigens, eliciting a protective immune response. Methods: Purified parasitophorous vacuole membrane-enclosed merozoite structures (PEMSs) containing native schizont antigens are initially generated, separated by two-dimensional (2D) gel electrophoresis and blotted onto nitrocellulose. Antigens eliciting a protective antibody response are visualized by incubation with sera from patients with clinical immunity. This is followed by the elution of low-affinity antibodies with urea and detection of protective antibody responses by incubation with anti-IgG1 and anti-IgG3 antibodies, which were conjugated to horseradish peroxidase. This is followed by visualization with a color reaction. Blot signals are normalized by relating to the intensity of blot staining with a reference antibody and housekeeping antigens. Results are corrected for intensity of exposure by the relation of antibody responses to global P. falciparum antibody titers. Antigens eliciting the protective responses are identified as immunorelevant from the comparison of spot positions, indicating high-affinity IgG1 or IgG3 responses on the western blot, which is unique to or consistently more intensive in clinically immune individuals compared with nonimmune individuals. The results obtained are validated by using affinity chromatography. Results: Another group previously applied 2D western blotting to analyze antibody responses to P. falciparum. The sera of patients allowed the detection of 42 antigenic spots on the 2D immunoblot. The spots detected were excised and subjected to mass spectrometry for identification. A total of 19 protein spots were successfully identified and corresponded to 13 distinct proteins. Another group used immunoaffinity chromatography to identify antigens bound by IgGs produced by mice with enhanced immunity to Plasmodium yoelii. Immunorelevant antigens were isolated and identified by immobilizing immunoglobulin from immune mice to a Sephadex column and then passing a blood-stage antigen mixture through the column followed by the elution of specific bound antigens with sodium deoxycholate and the identification of those antigens by western blotting with specific antibodies. Conclusions: 2D western blotting using native antigens has the potential to identify antibody responses selective for specific defined isomeric forms of the same protein, including isoforms (protein species) generated by posttranscriptional modifications such as phosphorylation, glycosylation, and methylation. The process involved in 2D western blotting enables highly sensitive detection, high resolution, and preservation of antibody responses during blotting. Validation by immunoaffinity chromatography can compensate for the antigen loss associated with the blotting process. It has the potential for indirect quantification of protective antibody responses by enabling quantification of the amount of eluted antibody bound antigens through mass spectrometry. International registered report identifier (irrid): PRR1-10.2196/15690.
Language	English
Publishing date	2020-07-17
Publishing country	Canada
Document type	Journal Article
ZDB-ID	2719222-2
ISSN	1929-0748
ISSN	1929-0748
DOI	10.2196/15690
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Article: Evidence Supporting the Hypothesis That Inflammation-Induced Vasospasm Is Involved in the Pathogenesis of Acquired Sensorineural Hearing Loss.

Eisenhut, Michael

International journal of otolaryngology

2019 Volume 2019, Page(s) 4367240

Abstract: Sensorineural hearing loss is mainly acquired and affects an estimated 1.3 billion humans worldwide. It is related to aging, noise, infection, ototoxic drugs, and genetic defects. It is essential to identify reversible and preventable causes to be able ... ...

Abstract	Sensorineural hearing loss is mainly acquired and affects an estimated 1.3 billion humans worldwide. It is related to aging, noise, infection, ototoxic drugs, and genetic defects. It is essential to identify reversible and preventable causes to be able to reduce the burden of this disease. Inflammation is involved in most causes and leads to tissue injury through vasospasm-associated ischemia. Vasospasm is reversible. This review summarized evidence linking inflammation-induced vasospasm to several forms of acquired sensorineural hearing loss. The link between vasospasm and sensorineural hearing loss is directly evident in subarachnoid haemorrhage, which involves the release of vasoconstriction-inducing cytokines like interleukin-1, endothelin-1, and tumour necrosis factor. These proinflammatory cytokines can also be released in response to infection, autoimmune disease, and acute or chronically increased inflammation in the ageing organism as in presbyacusis or in noise-induced cochlear injury. Evidence of vasospasm and hearing loss has also been discovered in bacterial meningitis and brain injury. Resolution of inflammation-induced vasospasm has been associated with improvement of hearing in autoimmune diseases involving overproduction of interleukin-1 from inflammasomes. There is mainly indirect evidence for vasospasm-associated sensorineural hearing loss in most forms of systemic or injury- or infection-induced local vascular inflammation. This opens up avenues in prevention and treatment of vascular and systemic inflammation as well as vasospasm itself as a way to prevent and treat most forms of acquired sensorineural hearing loss. Future research needs to investigate interventions antagonising vasospasm and vasospasm-inducing proinflammatory cytokines and their production in randomised controlled trials of prevention and treatment of acquired sensorineural hearing loss. Prime candidates for interventions are hereby inflammasome inhibitors and vasospasm-reducing drugs like nitric oxide donors, rho-kinase inhibitors, and magnesium which have the potential to reduce sensorineural hearing loss in meningitis, exposure to noise, brain injury, arteriosclerosis, and advanced age-related and autoimmune disease-related inflammation.
Language	English
Publishing date	2019-11-06
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	2503281-1
ISSN	1687-921X ; 1687-9201
ISSN (online)	1687-921X
ISSN	1687-9201
DOI	10.1155/2019/4367240
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Article: Stimulation of Nucleotide Oligomerization Domain and Toll-Like Receptors 2 to Enhance the Effect of Bacillus Calmette Guerin Immunization for Prevention of Mycobacterium Tuberculosis Infection: Protocol for a Series of Preclinical Randomized Controlled Trials.

Eisenhut, Michael

JMIR research protocols

2019 Volume 8, Issue 6, Page(s) e13045

Abstract: Background: Bacillus calmette guerin (BCG) immunization has been associated with a reduction in Mycobacterium tuberculosis (MTB) infection. BCG immunization has been shown to enhance innate immunity. This effect of BCG can be explained by an enhancing ... ...

Abstract	Background: Bacillus calmette guerin (BCG) immunization has been associated with a reduction in Mycobacterium tuberculosis (MTB) infection. BCG immunization has been shown to enhance innate immunity. This effect of BCG can be explained by an enhancing effect on innate immunity. Objective: This study aimed to test the following hypotheses: (1) BCG immunization can prevent infection with MTB, (2) prevention of infection occurs via stimulation of NOD2 (nucleotide oligomerization domain) and toll-like receptors 2 (TLR2), and (3) the effect of BCG immunization on prevention of infection with MTB can be enhanced by giving stimulators of NOD2 and TLR2. Methods: To detect the influence of immunization on infection rates, the ultralow dose (ULD) infection model is used. The infection rate of mice vaccinated with BCG and exposed after 6 weeks to ULD of MTB and unvaccinated mice are compared via cultures of lung homogenates and interferon (IFN) gamma release assay. If a reduced infection rate by BCG immunization is confirmed, the experiment is repeated by giving BCG combined simultaneously or in time sequence with the enhancers of innate immunity murabutide or beta-glycan. The influence of murabutide or beta-glycan alone on infection rates is investigated. To quantify the contribution of innate immunity levels of tumor necrosis factor, IFN gamma expression, histone H3 K4me3 trimethylation, and concentrations of monocytes with features of activation of innate immunity as defined by the Ly6Chigh as well as CD11b positive phenotype in immunized versus unimmunized infected and uninfected mice in the various immunization protocols is compared. The experiments will be repeated with prior application of the inhibitors of epigenetic programming of innate immunity histone methyltransferase inhibitor 5'-deoxy-5'-methylthio-adenosine and histone acetyl transferase inhibitor epigallocatechin-3-gallate. The influence of BCG on innate immunity is further corroborated by a prospective observational study in human infants. Results: Investigations of derivatives of muramyl dipeptide (MDP) to enhance early immunity in the C57BL/6 mouse strain (mice aged 7 weeks) by another group used 300 micrograms per mouse of oil-associated 6-0-mycoloyl-N-acetylmuramyl-L-alanyl-D-isoglutamine (mycol-MDP) 50/50 mixed with Freund's incomplete adjuvant. Comparison of colony-forming unit (CFU) count in the lungs 3 weeks after aerosol challenge with Mycobacterium bovis of groups (n=5) between groups receiving mycol-MDP in oil emulsion (see above) versus controls (n=5) showed a significantly lower CFU count of 94.5 x106 (SD 22.0) in cases versus controls with 204.0 X 106 (SD 77.6). It is important to note that after elimination of T-cells in this model, a reduction of CFU in lungs of mice treated with mycol-MDP persisted albeit without statistical significance, which was possibly related to the small number of animals used. Conclusions: Demonstration of a reduction of MTB infection by enhancement of innate immunity could show a new approach to improving vaccine efficacy against this pathogen. International registered report identifier (irrid): PRR1-10.2196/13045.
Language	English
Publishing date	2019-06-08
Publishing country	Canada
Document type	Journal Article
ZDB-ID	2719222-2
ISSN	1929-0748
ISSN	1929-0748
DOI	10.2196/13045
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Article ; Online: The Potential Role of Steroid-Induced Cerebral Vasospasm in the Pathogenesis of Delayed Cerebral Injury in Bacterial Meningitis.

Eisenhut, Michael

Critical care medicine

2018 Volume 46, Issue 8, Page(s) 1383–1384

MeSH term(s)	Adult ; Brain Injuries ; Humans ; Meningitis, Bacterial ; Subarachnoid Hemorrhage ; Vasospasm, Intracranial
Language	English
Publishing date	2018-07-13
Publishing country	United States
Document type	Journal Article ; Comment
ZDB-ID	197890-1
ISSN	1530-0293 ; 0090-3493
ISSN (online)	1530-0293
ISSN	0090-3493
DOI	10.1097/CCM.0000000000003228
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Article ; Online: In diabetic ketoacidosis brain injury including cerebral oedema and infarction is caused by interleukin-1.

Eisenhut, Michael

Medical hypotheses

2018 Volume 121, Page(s) 44–46

Abstract: Background: Brain injury in diabetic ketoacidosis (DKA) is common but under recognized and affects up to 54% of patients with this complication. It's manifestations include cerebral oedema (CE) and cerebral infarction (CI). The etiology of CE in DKA has ...

Abstract	Background: Brain injury in diabetic ketoacidosis (DKA) is common but under recognized and affects up to 54% of patients with this complication. It's manifestations include cerebral oedema (CE) and cerebral infarction (CI). The etiology of CE in DKA has up to the present time been uncertain. Practical management had been guided by the assumption that rapid osmotic shifts due to rapid correction of hypovolemia and reduction of plasma glucose could cause a shift of water into the cells. The osmotic effect of glucose can cause inflammation by activation of inflammasomes. Recently it has been recognized that the body is in a pro-inflammatory state during DKA involving interleukin-1 production by inflammasomes. Interleukin-1 has been involved in the pathogenesis of cerebral oedema and CI. Hypothesis: In diabetic ketoacidosis brain injury including cerebral oedema and infarction is caused by interleukin-1. Confirmation of hypothesis and implications: Inflammasome activity could be quantified in peripheral blood mononuclear cells and in patients with and without clinical and/or subclinical CE and/or stroke or features of cerebral ischemia on MRI. Surrogates of brain injury in peripheral blood like neuron specific enolase could be measured and correlated with inflammasome activity. Interleukin-1 receptor antagonists and inflammasome inhibitors including telmisartan could be assessed in their effect on MRI changes consistent with CE or CI in patients with DKA in randomised placebo-controlled trials.
MeSH term(s)	Animals ; Blood Glucose/analysis ; Brain Edema/immunology ; Brain Edema/pathology ; Brain Infarction/immunology ; Brain Injuries/complications ; Diabetic Ketoacidosis/immunology ; Diabetic Ketoacidosis/pathology ; Hippocampus/metabolism ; Humans ; Infarction ; Inflammation ; Interleukin 1 Receptor Antagonist Protein/metabolism ; Interleukin-1/immunology ; Leukocytes, Mononuclear/cytology ; Magnetic Resonance Imaging ; Mice ; Models, Theoretical ; Osmosis
Chemical Substances	Blood Glucose ; Interleukin 1 Receptor Antagonist Protein ; Interleukin-1
Language	English
Publishing date	2018-09-06
Publishing country	United States
Document type	Journal Article
ZDB-ID	193145-3
ISSN	1532-2777 ; 0306-9877
ISSN (online)	1532-2777
ISSN	0306-9877
DOI	10.1016/j.mehy.2018.09.005
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Article: Commentary: Cytokine-Regulation of Na

Eisenhut, Michael

Frontiers in immunology

2017 Volume 8, Page(s) 1490

Language	English
Publishing date	2017
Publishing country	Switzerland
Document type	Journal Article ; Comment
ZDB-ID	2606827-8
ISSN	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2017.01490
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Article ; Online: The Identification of Native Epitopes Eliciting a Protective High-Affinity Immunoglobulin Subclass Response to Blood Stages of Plasmodium falciparum

Eisenhut, Michael

JMIR Research Protocols, Vol 9, Iss 7, p e

Protocol for Observational Studies

2020 Volume 15690

Abstract: BackgroundAntibodies to blood stages protective against complications of Plasmodium falciparum infection were found to be of immunoglobulin G 1 (IgG1) and IgG3 subclasses and of high affinity to the target epitopes. These target epitopes cannot be ... ...

Abstract	BackgroundAntibodies to blood stages protective against complications of Plasmodium falciparum infection were found to be of immunoglobulin G 1 (IgG1) and IgG3 subclasses and of high affinity to the target epitopes. These target epitopes cannot be characterized using recombinant antigens because of a lack of appropriate glycosylation, phosphorylation, methylation, and bisulfide bond formation, which determine the structure of conformational and nonlinear epitopes within the tertiary and quaternary structures of native P. falciparum antigens. ObjectiveThis study aims to develop a method for the comprehensive detection of all P. falciparum schizont antigens, eliciting a protective immune response. MethodsPurified parasitophorous vacuole membrane–enclosed merozoite structures (PEMSs) containing native schizont antigens are initially generated, separated by two-dimensional (2D) gel electrophoresis and blotted onto nitrocellulose. Antigens eliciting a protective antibody response are visualized by incubation with sera from patients with clinical immunity. This is followed by the elution of low-affinity antibodies with urea and detection of protective antibody responses by incubation with anti-IgG1 and anti-IgG3 antibodies, which were conjugated to horseradish peroxidase. This is followed by visualization with a color reaction. Blot signals are normalized by relating to the intensity of blot staining with a reference antibody and housekeeping antigens. Results are corrected for intensity of exposure by the relation of antibody responses to global P. falciparum antibody titers. Antigens eliciting the protective responses are identified as immunorelevant from the comparison of spot positions, indicating high-affinity IgG1 or IgG3 responses on the western blot, which is unique to or consistently more intensive in clinically immune individuals compared with nonimmune individuals. The results obtained are validated by using affinity chromatography. ResultsAnother group previously applied 2D western blotting to analyze ...
Keywords	Medicine ; R ; Computer applications to medicine. Medical informatics ; R858-859.7
Subject code	616
Language	English
Publishing date	2020-07-01T00:00:00Z
Publisher	JMIR Publications
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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